Characterizing the NIH Activity and Chronicity Indices in 2 Independent Lupus Nephritis Cohorts

The inclusion of National Institutes of Health (NIH) activity index (AI) and chronicity index (CI) in the ISN/Renal Pathology Society (ISN/RPS) classification of lupus nephritis (LN) aims to provide a precise characterization of the amount of active and chronic lesions next to lupus class. We here investigate the distribution of NIH indices within 2 international LN cohorts, their relationship with the ISN/RPS classes and which lesions most significantly contribute to these scores.

We collected 194 biopsies from 2 cohorts of patients with LN and calculated the NIH AI and CI according to the revised 2018 ISN/RPS classification. For statistical analysis we mainly used nonparametric tests. An exploratory factor analysis was applied to the lesion scores.

The NIH AI score was usually medium-low, reaching a maximum value of 16 of 24, whereas the NIH CI reached 10 of 12. Both indices were higher in classes III, IV, and mixed compared with others (P < 0.0001). Endocapillary hypercellularity was present in > 70% of biopsies, showing a strong correlation with neutrophils/karyorrhexis (r = 0.78, P < 0.0001) and cellular crescents (P < 0.0001). Chronic lesions showed a strong correlation with each other (P < 0.0001), except for fibrous crescents which had the strongest correlation with cellular crescents (r = 0.33, P < 0.0001). The inclusion of all lesions in an exploratory factor analysis uncovered 2 underlying main factors that accurately reflect the NIH AI and CI.

This study revealed key aspects of the NIH AI and CI that may guide future modifications of these indices, leading to a more balanced and reliable scoring system.